Project Summary: Dr. Brendan Lucey, MD is a highly-motivated physician-scientist with a strong interest in sleep, aging, and neurodegenerative disorders such as Alzheimer?s disease. He is an Assistant Professor of Neurology (tenure track) at Washington University and is seeking support from this administrative supplement for research costs to explore novel changes in cerebrospinal fluid (CSF) tau, phosphorylated tau (p-tau), and ?-synuclein concentrations with sleep-wake activity and pharmacologic sleep induction via orexin receptor antagonism from suvorexant. Dr. Lucey?s long-term goal is to develop an exciting research program investigating the interrelationships between sleep, aging, and Alzheimer?s disease. Understanding these relationships could drive the development of new treatments to prevent or delay Alzheimer?s disease. This administrative supplement request builds on recently published work and our unpublished preliminary data showing that sleep loss increases concentrations of tau and ?-synuclein in cerebrospinal fluid (CSF) and affects the forms of phosphorylated tau (p-tau). Further, this supplement will leverage novel samples collected as part of the parent grant.